Frontiers in virology最新文献

Significant progress has been made in enhancing recombinant adeno-associated virus (rAAV) for clinical investigation. Despite its versatility as a gene delivery platform, the inherent packaging constraint of 4.7 kb imposes restrictions on the range of diseases it can address. In this context, we present findings of an exceptionally compact and long-term promoter that facilitates the expression of larger genes compared to conventional promoters. This compact promoter originated from the genome of the alphaherpesvirus pseudorabies virus, latency-associated promoter 2 (LAP2, 404 bp). Promoter driving an mCherry reporter was packaged into single strand (ss) AAV8 and AAV9 vectors and injected into adult C57BL/6 mice at a dose of 5 x 1011 vg/mouse by single intravenous or intramuscular administration. An ssAAV8 and ssAAV9 vector with elongation factor-1α promoter (EF1α, 1264 bp) was injected side-by-side for comparison. After 400 days, we sacrificed the mice and examined mCherry expression in liver, kidney, heart, lung, spleen, pancreas, skeletal muscle, and brain. We found that LAP2 exhibited robust transgene expression across a wide range of cells and tissues comparable to the larger EF1α, which is currently recognized as a rather potent and ubiquitous promoter. The AAV8-LAP2 and AAV9-LAP2 constructs displayed strong transduction and transcription in liver, kidney, and skeletal muscle on both route of administration. However, no expression was detected in the heart, lung, spleen, pancreas, and brain. The outcomes of our investigation propose the viability of LAP2 for gene therapy applications demanding the expression of large or multiple therapeutic genes following a single viral-vector administration.

Hepatitis C virus (HCV) is a well-known virus that causes liver diseases such as liver cirrhosis and hepatocellular carcinoma. For several decades, numerous studies have been conducted to unravel the life cycle and molecular mechanisms of this virus with the aim of developing strategies to combat diseases caused by its infection. In this review, we summarize HCV assembly to budding, focusing on one of the structural proteins, the core, a viral capsid that binds both the viral genome and host membrane, along with the core-interacting host partners. The HCV core matures in the endoplasmic reticulum (ER), localizes at the lipid droplet (LD), and shuttles between the LD and ER to form viral particles. This process is controlled by many host factors known to binds core proteins, such as diacylglycerol acyltransferase-1 (DGAT-1), Rab18, μ subunit of the clathrin adaptor protein complex 2 (AP2M1), nuclear pore complex protein 98 (Nup98), Cortactin, group IVA phospholipase A2 (PLA2G4A) etc. Virion budding is thought to involve contributions from endosomal sorting complexes required for transport (ESCRT), similar to other envelope viruses. We delved into potential perspectives to enhance our understanding of the HCV mechanism by drawing insights from existing studies.

Long COVID (also termed Post-acute sequelae of COVID-19 [PASC]) refers to the chronic symptoms that survivors may experience after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and acute coronavirus disease 2019 (COVID-19) disease. Long COVID represents a global public health, medical, and nursing challenge that affects millions of people. As an emerging and evolving syndrome, long COVID manifests with many combinations of clinical signs and symptoms that healthcare providers and scientists are cataloging and struggling to understand. In this mini-review, we introduce the epigenetic battlefield of DNA methylation (DNAm) on which the virus and the host interact. We suggest ways in which DNAm phenomena and markers induced by this virus-host interaction may help clarify the pathology and prognosis of long COVID. Knowledge of DNAm characteristics of long COVID patients is limited as of this writing (early-2024), investigators have noted both the partial reversibility and the potential long-lasting persistence of the DNAm markers induced by acute COVID-19. Long-term sequelae seen in other coronavirus diseases such as severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) are potential references for long COVID in an effort towards more precise diagnosis and disease characterization, better prediction of outcomes, and the use of epigenetic phenomena towards development of new drugs and immunotherapies.

Enveloped viruses complete their replication cycle by forming virions that bud from infected cells through membrane scission. The mechanisms by which this is achieved are less well-understood than the well-characterized membrane scission of vesicles budding inwards into the cytosol. The scission of vesicles that bud away from the cytosol is mediated by machinery of the endosomal sorting complexes required for transport (ESCRT)-III, which is highjacked by viruses of several different families. Other groups of viruses can bud independently of ESCRT-III activity. It has not been fully elucidated how the latter achieve this in the absence of host ESCRT-III, but it is known that some viral proteins directly mediate membrane scission. The Herpesviridae constitute a family of highly diverse viruses that bud at the inner nuclear membrane and cytoplasmic membranes in infected cells. Many investigators have attempted to determine the mechanism of membrane scission during herpesvirus budding, and have found this to be complex, not exactly conforming to either of the two methods. The present review attempts to synthesize the disparate findings into a model of herpesvirus egress based on both ESCRT-mediated and viral protein-mediated mechanisms.

The past decade has seen the global reemergence and rapid spread of enterovirus D68 (EV-D68), a respiratory pathogen that causes severe respiratory illness and paralysis in children. EV-D68 was first isolated in 1962 from children with pneumonia. Sporadic cases and small outbreaks have been reported since then with a major respiratory disease outbreak in 2014 associated with an increased number of children diagnosed with polio-like paralysis. From 2014-2018, major outbreaks were reported every other year in a biennial pattern with > 90% of the cases occurring in children under the age of 16. With the outbreak of SARS-CoV-2 and the subsequent COVID-19 pandemic, there was a significant decrease in the prevalence EV-D68 cases along with other respiratory diseases. However, since the relaxation of pandemic social distancing protocols and masking mandates the number of EV-D68 cases have begun to rise again-culminating in another outbreak in 2022. Here we review the virology, pathogenesis, and the immune response to EV-D68, and discuss the epidemiology of EV-D68 infections and the divergence of contemporary strains from historical strains. Finally, we highlight some of the key challenges in the field that remain to be addressed.